Anti-androgens Compared: Cyproterone Acetate, Spironolactone, GnRH Agonists and Bicalutamide in Feminising Hormone Therapy

An evidence review comparing the anti-androgens used alongside oestrogen in feminising hormone therapy — cyproterone acetate, spironolactone, GnRH agonists and bicalutamide — grading each on mechanism, efficacy and safety rather than ranking them. The central finding is that comparative feminising efficacy is barely evidenced: no adequately powered trial ranks the agents across the outcomes that matter, and the single head-to-head randomised trial found no difference in breast development between cyproterone acetate and spironolactone despite cyproterone suppressing testosterone significantly more. A methodological thread runs throughout — total serum testosterone is a poor surrogate for a receptor-level blocker, illustrated most strongly by bicalutamide, which is associated with breast development while testosterone remains high. The review grades each agent's principal safety signal (cyproterone and meningioma; spironolactone and potassium; the favourable but cost-limited GnRH agonists; bicalutamide and hepatotoxicity), sets out the effects of androgen blockade on skin and hair, and concludes that anti-androgen selection is a safety-and-practicality decision matched to the individual rather than a ranking. Certainty is graded per claim; data extrapolated from cisgender or adolescent populations are flagged.